Differential effects of interleukin-1 receptor antagonist and tumor necrosis factor binding protein on fatty-streak formation in apolipoprotein E-deficient mice.
BACKGROUND
The cytokines interleukin 1 (IL-1) and tumor necrosis factor (TNF) are secreted by the different cell populations of the vascular wall and have been suggested to promote atherosclerosis.


RESULTS
Their respective roles in fatty-streak formation in apolipoprotein E-deficient mice were investigated by use of IL-1 receptor antagonist and TNF binding protein. Estradiol-17beta was used as a positive control. Blocking TNF seemed to be active in female animals but not in males. IL-1 receptor antagonist was as effective as or more effective than estradiol in both sexes.


CONCLUSIONS
IL-1 plays a crucial role in the initial step of the atherosclerotic process in this animal model, and blocking the activity of this cytokine should be considered as a therapeutic possibility.
Elhage
R
R
INSERM U397, Institut L. Bugnard, CHU Rangueil, Toulouse, France.
Maret
A
A
Pieraggi
M T
MT
Thiers
J C
JC
Arnal
J F
JF
Bayard
F
F
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D001161:Arteriosclerosis / Q000209:etiology* / Q000473:pathology; D002352:Carrier Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D053590:Interleukin 1 Receptor Antagonist Protein; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D012795:Sialoglycoproteins / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D053319:Tumor Necrosis Factor Decoy Receptors
D001057:Apolipoproteins E; D002352:Carrier Proteins; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D012795:Sialoglycoproteins; D053319:Tumor Necrosis Factor Decoy Receptors; C069521:recombinant human tumor necrosis factor-binding protein-1; D004958:Estradiol